Acquiring nerve activity from carotid body and/or sinus

ABSTRACT

An exemplary includes acquiring an electroneurogram of the right carotid sinus nerve or the left carotid sinus nerve, analyzing the electroneurogram for at least one of chemosensory information and barosensory information and calling for one or more therapeutic actions based at least in part on the analyzing. Therapeutic actions may aim to treat conditions such as sleep apnea, an increase in metabolic demand, hypoglycemia, hypertension, renal failure, and congestive heart failure. Other exemplary methods, devices, systems, etc., are also disclosed.

PRIORITY CLAIM

This application is a Continuation Application of and claims priorityand other benefits from U.S. patent application Ser. No. 12/833,170,filed Jul. 9, 2010, entitled “ACQUIRING NERVE ACTIVITY FROM CAROTID BODYAND/OR SINUS”, now U.S. Pat. No. 7,953,479, incorporated herein byreference in its entirety.

TECHNICAL FIELD

Subject matter presented herein generally relates to techniques toacquire nerve activity from the carotid body and/or sinus for purposesof diagnostics and/or therapy.

BACKGROUND

The ninth cranial nerve (CN IX), referred to as the glossopharyngealnerve, includes a branch that innervates the carotid body and carotidsinus. This branch is referred to as the carotid sinus nerve (CSN),which occurs bilaterally (i.e., right CSN and left CSN). The CSNincludes afferent fibers that convey information about arterial bloodgoing to the brain. In particular, the CSN conveys chemosensoryinformation and barosensory information. Such information can be usefulalone or in conjunction with other information to treat a variety ofconditions. Various techniques are described herein for acquisition,analysis and use of CSN information. Such techniques are optionallyimplemented in conjunction with one or more respiratory, cardiac ormetabolic therapies.

SUMMARY

An exemplary includes acquiring an electroneurogram of the right carotidsinus nerve or the left carotid sinus nerve, analyzing theelectroneurogram for at least one of chemosensory information andbarosensory information and calling for one or more therapeutic actionsbased at least in part on the analysis. Therapeutic actions may aim totreat conditions such as sleep apnea, an increase in metabolic demand,hypoglycemia, hypertension, renal failure, and heart failure. Otherexemplary methods, devices, systems, etc., are also disclosed.

In general, the various methods, devices, systems, etc., describedherein, and equivalents thereof, are optionally suitable for use in avariety of pacing therapies, other cardiac related therapies, etc.

BRIEF DESCRIPTION OF THE DRAWINGS

Features and advantages of the described implementations can be morereadily understood by reference to the following description taken inconjunction with the accompanying drawings.

FIG. 1 is a simplified diagram illustrating an exemplary implantablestimulation device in electrical communication with three leadsimplanted into a patient's heart and at least one other leadpositionable proximate to an upper airway muscle or nerve. An exemplarydevice may have more leads or fewer leads.

FIG. 2 is a functional block diagram of an exemplary implantablestimulation device illustrating basic elements that are configured toprovide cardioversion, defibrillation, pacing stimulation or othertissue or nerve stimulation. The implantable stimulation device isfurther configured to sense information and administer stimulationpulses responsive to such information.

FIG. 3 is an approximate anatomic diagram that includes the right andleft carotid body and sinus and an exemplary method for acquiring nerveinformation.

FIG. 4 is an approximate anatomical diagram related to anatomy of theright cervical region and pathways from the carotid body and sinus tothe solitary nucleus.

FIG. 5 is an approximate anatomical diagram of a unit of the carotidbody responsive to chemical changes.

FIG. 6 is a block diagram of various exemplary scenarios for acquiringnerve information, analyzing the information, and acting on theinformation.

FIG. 7 is a block diagram of scenarios I and III of FIG. 6.

FIG. 8 is a block diagram of scenario II of FIG. 6.

FIG. 9 is a series of block diagrams for various exemplary methods andarrangements for implementing methods that can facilitate analysis ofnerve activity.

FIG. 10 is a block diagram of various exemplary methods for diagnosingconditions and optional control actions based at least in part on adiagnosis.

FIG. 11 is a block diagram of an exemplary method for delivering noiseto a nerve and acquiring information from the nerve.

DETAILED DESCRIPTION

The following description includes the best mode presently contemplatedfor practicing the described implementations. This description is not tobe taken in a limiting sense, but rather is made merely for the purposeof describing the general principles of the implementations. The scopeof the described implementations should be ascertained with reference tothe issued claims. In the description that follows, like numerals orreference designators will be used to reference like parts or elementsthroughout.

Overview

Various exemplary methods, devices, systems, etc., described hereinpertain acquiring nerve information for the right and/or left carotidsinus nerve (CSN) (also known as Hering's nerve), which is a branch ofthe ninth cranial nerve (CN IX), also known as the glossopharyngealnerve (GPN). The right and left CSN include afferent fibers that conveyinformation from a respective carotid body and carotid sinus to thebrain. Information carried by the CSN includes chemical information aswell as pressure information. Various exemplary technologies acquire CSNinformation (e.g., sensing nerve activity such as an electroneurogram,via data communication, etc.) and use the information for diagnosticsand/or therapy, optionally analyzing the information prior to use.

Exemplary Stimulation Device

FIG. 1 shows an exemplary stimulation device 100 in electricalcommunication with a patient's heart 102 by way of three leads 104, 106,108, suitable for delivering multi-chamber stimulation and shocktherapy. The leads 104, 106, 108 are optionally configurable fordelivery of stimulation pulses suitable for stimulation of autonomicnerves, non-myocardial tissue, other nerves, etc. In addition, thedevice 100 includes a fourth lead 110 having, in this implementation,three electrodes 144, 144′, 144″ suitable for sensing activity of and/orstimulation of autonomic nerves, non-myocardial tissue, other nerves,etc. For example, this lead may be positioned in and/or near a patient'sheart or near an autonomic nerve within a patient's body and remote fromthe heart. Various examples described herein include positioning a leadproximate to the right and/or the left carotid sinus nerve for at leastpurposes of sensing nerve activity.

The right atrial lead 104, as the name implies, is positioned in and/orpasses through a patient's right atrium. The right atrial lead 104optionally senses atrial cardiac signals and/or provide right atrialchamber stimulation therapy. As shown in FIG. 1, the stimulation device100 is coupled to an implantable right atrial lead 104 having, forexample, an atrial tip electrode 120, which typically is implanted inthe patient's right atrial appendage. The lead 104, as shown in FIG. 1,also includes an atrial ring electrode 121. Of course, the lead 104 mayhave other electrodes as well. For example, the right atrial leadoptionally includes a distal bifurcation having electrodes suitable forsensing activity of and/or stimulating autonomic nerves, non-myocardialtissue, other nerves, etc.

To sense atrial cardiac signals, ventricular cardiac signals and/or toprovide chamber pacing therapy, particularly on the left side of apatient's heart, the stimulation device 100 is coupled to a coronarysinus lead 106 designed for placement in the coronary sinus and/ortributary veins of the coronary sinus. Thus, the coronary sinus lead 106is optionally suitable for positioning at least one distal electrodeadjacent to the left ventricle and/or additional electrode(s) adjacentto the left atrium. In a normal heart, tributary veins of the coronarysinus include, but may not be limited to, the great cardiac vein, theleft marginal vein, the left posterior ventricular vein, the middlecardiac vein, and the small cardiac vein.

Accordingly, an exemplary coronary sinus lead 106 is optionally designedto receive atrial and ventricular cardiac signals and to deliver leftventricular pacing therapy using, for example, at least a leftventricular tip electrode 122, left atrial pacing therapy using at leasta left atrial ring electrode 124, and shocking therapy using at least aleft atrial coil electrode 126. For a complete description of a coronarysinus lead, the reader is directed to U.S. Pat. No. 5,466,254, “CoronarySinus Lead with Atrial Sensing Capability” (Helland), which isincorporated herein by reference. The coronary sinus lead 106 furtheroptionally includes electrodes for stimulation of autonomic nerves. Sucha lead may include pacing and autonomic nerve stimulation functionalityand may further include bifurcations or legs. For example, an exemplarycoronary sinus lead includes pacing electrodes capable of deliveringpacing pulses to a patient's left ventricle and at least one electrodecapable of stimulating an autonomic nerve. An exemplary coronary sinuslead (or left ventricular lead or left atrial lead) may also include atleast one electrode capable of sensing activity of and/or stimulating anautonomic nerve, non-myocardial tissue, other nerves, etc., wherein suchan electrode may be positioned on the lead or a bifurcation or leg ofthe lead.

Stimulation device 100 is also shown in electrical communication withthe patient's heart 102 by way of an implantable right ventricular lead108 having, in this exemplary implementation, a right ventricular tipelectrode 128, a right ventricular ring electrode 130, a rightventricular (RV) coil electrode 132, and an SVC coil electrode 134.Typically, the right ventricular lead 108 is transvenously inserted intothe heart 102 to place the right ventricular tip electrode 128 in theright ventricular apex so that the RV coil electrode 132 will bepositioned in the right ventricle and the SVC coil electrode 134 will bepositioned in the superior vena cava. Accordingly, the right ventricularlead 108 is capable of sensing or receiving cardiac signals, anddelivering stimulation in the form of pacing and shock therapy to theright ventricle. An exemplary right ventricular lead may also include atleast one electrode capable of sensing activity of and/or stimulating anautonomic nerve, non-myocardial tissue, other nerves, etc., wherein suchan electrode may be positioned on the lead or a bifurcation or leg ofthe lead.

FIG. 2 shows an exemplary, simplified block diagram depicting variouscomponents of stimulation device 100. The stimulation device 100 can becapable of treating both fast and slow arrhythmias with stimulationtherapy, including cardioversion, defibrillation, and pacingstimulation. The stimulation device can be solely or further capable ofdelivering stimuli to autonomic nerves, non-myocardial tissue, othernerves, etc. While a particular multi-chamber device is shown, it is tobe appreciated and understood that this is done for illustrationpurposes only. Thus, the techniques and methods described below can beimplemented in connection with any suitably configured or configurablestimulation device. Accordingly, one of skill in the art could readilyduplicate, eliminate, or disable the appropriate circuitry in anydesired combination to provide a device capable of treating theappropriate chamber(s) or regions of a patient's heart withcardioversion, defibrillation, pacing stimulation, autonomic nervestimulation, non-myocardial tissue stimulation, other nerve stimulation,etc.

Housing 200 for stimulation device 100 is often referred to as the“can”, “case” or “case electrode”, and may be programmably selected toact as the return electrode for all “unipolar” modes. Housing 200 mayfurther be used as a return electrode alone or in combination with oneor more of the coil electrodes 126, 132 and 134 for shocking purposes.Housing 200 further includes a connector (not shown) having a pluralityof terminals 201, 202, 204, 206, 208, 212, 214, 216, 218, 221 (shownschematically and, for convenience, the names of the electrodes to whichthey are connected are shown next to the terminals).

To achieve right atrial sensing and/or pacing, the connector includes atleast a right atrial tip terminal (A_(R) TIP) 202 adapted for connectionto the atrial tip electrode 120. A right atrial ring terminal (A_(R)RING) 201 is also shown, which is adapted for connection to the atrialring electrode 121. To achieve left chamber sensing, pacing and/orshocking, the connector includes at least a left ventricular tipterminal (V_(L) TIP) 204, a left atrial ring terminal (A_(L) RING) 206,and a left atrial shocking terminal (A_(L) COIL) 208, which are adaptedfor connection to the left ventricular tip electrode 122, the leftatrial ring electrode 124, and the left atrial coil electrode 126,respectively. Connection to suitable autonomic nerve stimulationelectrodes or other tissue stimulation or sensing electrodes is alsopossible via these and/or other terminals (e.g., via a nerve and/ortissue stimulation and/or sensing terminal S ELEC 221).

To support right chamber sensing, pacing, and/or shocking, the connectorfurther includes a right ventricular tip terminal (V_(R) TIP) 212, aright ventricular ring terminal (V_(R) RING) 214, a right ventricularshocking terminal (RV COIL) 216, and a superior vena cava shockingterminal (SVC COIL) 218, which are adapted for connection to the rightventricular tip electrode 128, right ventricular ring electrode 130, theRV coil electrode 132, and the SVC coil electrode 134, respectively.Connection to suitable autonomic nerve stimulation electrodes or othertissue stimulation or sensing electrodes is also possible via theseand/or other terminals (e.g., via a nerve and/or tissue stimulationand/or sensing terminal S ELEC 221).

At the core of the stimulation device 100 is a programmablemicrocontroller 220 that controls the various modes of stimulationtherapy. As is well known in the art, microcontroller 220 typicallyincludes a microprocessor, or equivalent control circuitry, designedspecifically for controlling the delivery of stimulation therapy, andmay further include RAM or ROM memory, logic and timing circuitry, statemachine circuitry, and I/O circuitry. Typically, microcontroller 220includes the ability to process or monitor input signals (data orinformation) as controlled by a program code stored in a designatedblock of memory. The type of microcontroller is not critical to thedescribed implementations. Rather, any suitable microcontroller 220 maybe used that carries out the functions described herein. The use ofmicroprocessor-based control circuits for performing timing and dataanalysis functions are well known in the art.

Representative types of control circuitry that may be used in connectionwith the described embodiments can include the microprocessor-basedcontrol system of U.S. Pat. No. 4,940,052 (Mann et al.), thestate-machine of U.S. Pat. No. 4,712,555 (Thornander et al.) and U.S.Pat. No. 4,944,298 (Sholder), all of which are incorporated by referenceherein. For a more detailed description of the various timing intervalsused within the stimulation device and their inter-relationship, seeU.S. Pat. No. 4,788,980 (Mann et al.), also incorporated herein byreference.

FIG. 2 also shows an atrial pulse generator 222 and a ventricular pulsegenerator 224 that generate pacing stimulation pulses for delivery bythe right atrial lead 104, the coronary sinus lead 106, and/or the rightventricular lead 108 via an electrode configuration switch 226. It isunderstood that in order to provide stimulation therapy in each of thefour chambers of the heart the atrial and ventricular pulse generators,222 and 224, may include dedicated, independent pulse generators,multiplexed pulse generators, or shared pulse generators. The pulsegenerators 222 and 224 are controlled by the microcontroller 220 viaappropriate control signals 228 and 230, respectively, to trigger orinhibit the stimulation pulses.

Microcontroller 220 further includes timing control circuitry 232 tocontrol the timing of the stimulation pulses (e.g., pacing rate,atrio-ventricular (AV) delay, atrial interconduction (A-A) delay, orventricular interconduction (V-V) delay, etc.) as well as to keep trackof the timing of refractory periods, blanking intervals, noise detectionwindows, evoked response windows, alert intervals, marker channeltiming, etc., which is well known in the art.

Microcontroller 220 further includes an arrhythmia detector 234, amorphology discrimination module 236, a capture detection module 237, aCSN module 238 and optionally an orthostatic compensator and a minuteventilation (MV) response module, the latter two are not shown in FIG.2. These components can be utilized by the stimulation device 100 fordetermining desirable times to administer various therapies, includingthose to reduce the effects of orthostatic hypotension. Theaforementioned components may be implemented in hardware as part of themicrocontroller 220, or as software/firmware instructions programmedinto the device and executed on the microcontroller 220 during certainmodes of operation.

The CSN module 238 may perform a variety of tasks related to, forexample, arterial blood chemical composition and/or arterial bloodpressure. This component can be utilized by the stimulation device 100in determining therapy in response to chemosensory and/or barosensoryinformation. The CSN module 238 may be implemented in hardware as partof the microcontroller 220, or as software/firmware instructionsprogrammed into the device and executed on the microcontroller 220during certain modes of operation. The CSN module 238 may optionallyimplement various exemplary methods described herein. The CSN module 238may interact with the physiological sensors 270, the impedance measuringcircuit 278 and optionally other modules. One or more of thephysiological sensors 270 are optionally external to a pulse generatoryet can provide information to the microcontroller 220.

The electronic configuration switch 226 includes a plurality of switchesfor connecting the desired electrodes to the appropriate I/O circuits,thereby providing complete electrode programmability. Accordingly,switch 226, in response to a control signal 242 from the microcontroller220, determines the polarity of the stimulation pulses (e.g., unipolar,bipolar, combipolar, etc.) by selectively closing the appropriatecombination of switches (not shown) as is known in the art.

Atrial sensing circuits 244 and ventricular sensing circuits 246 mayalso be selectively coupled to the right atrial lead 104, coronary sinuslead 106, and the right ventricular lead 108, through the switch 226 fordetecting the presence of cardiac activity in each of the four chambersof the heart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR.SENSE) sensing circuits, 244 and 246, may include dedicated senseamplifiers, multiplexed amplifiers, or shared amplifiers. Switch 226determines the “sensing polarity” of the cardiac signal by selectivelyclosing the appropriate switches, as is also known in the art. In thisway, the clinician may program the sensing polarity independent of thestimulation polarity. The sensing circuits (e.g., 244 and 246) areoptionally capable of obtaining information indicative of tissuecapture.

Each sensing circuit 244 and 246 preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables the device 100 to deal effectively withthe difficult problem of sensing the low amplitude signalcharacteristics of atrial or ventricular fibrillation.

The outputs of the atrial and ventricular sensing circuits 244 and 246are connected to the microcontroller 220, which, in turn, is able totrigger or inhibit the atrial and ventricular pulse generators 222 and224, respectively, in a demand fashion in response to the absence orpresence of cardiac activity in the appropriate chambers of the heart.Furthermore, as described herein, the microcontroller 220 is alsocapable of analyzing information output from the sensing circuits 244and 246 and/or the data acquisition system 252 to determine or detectwhether capture has occurred and to program a pulse, or pulses, inresponse to such determinations. The sensing circuits 244 and 246, inturn, receive control signals over signal lines 248 and 250 from themicrocontroller 220 for purposes of controlling the gain, threshold,polarization charge removal circuitry (not shown), and the timing of anyblocking circuitry (not shown) coupled to the inputs of the sensingcircuits, 244 and 246, as is known in the art.

For arrhythmia detection, the device 100 utilizes the atrial andventricular sensing circuits, 244 and 246, to sense cardiac signals todetermine whether a rhythm is physiologic or pathologic. In reference toarrhythmias, as used herein, “sensing” is reserved for the noting of anelectrical signal or obtaining data (information), and “detection” isthe processing (analysis) of these sensed signals and noting thepresence of an arrhythmia. The timing intervals between sensed events(e.g., P-waves, R-waves, and depolarization signals associated withfibrillation which are sometimes referred to as “F-waves” or“Fib-waves”) are then classified by the arrhythmia detector 234 of themicrocontroller 220 by comparing them to a predefined rate zone limit(i.e., bradycardia, normal, low rate VT, high rate VT, and fibrillationrate zones) and various other characteristics (e.g., sudden onset,stability, physiologic sensors, and morphology, etc.) in order todetermine the type of remedial therapy that is needed (e.g., bradycardiapacing, anti-tachycardia pacing, cardioversion shocks or defibrillationshocks, collectively referred to as “tiered therapy”).

Cardiac signals are also applied to inputs of an analog-to-digital (A/D)data acquisition system 252. The data acquisition system 252 isconfigured to acquire intracardiac electrogram signals, convert the rawanalog data into a digital signal, and store the digital signals forlater processing and/or telemetric transmission to an external device254. The data acquisition system 252 is coupled to the right atrial lead104, the coronary sinus lead 106, the right ventricular lead 108 and/orthe nerve or other tissue stimulation lead 110 through the switch 226 tosample cardiac signals and/or other signals across any pair of desiredelectrodes. The data acquisition system 252 is optionally configured tosense nerve activity and/or muscle activity from muscles other than theheart.

The microcontroller 220 is further coupled to a memory 260 by a suitabledata/address bus 262, wherein the programmable operating parameters usedby the microcontroller 220 are stored and modified, as required, inorder to customize the operation of the stimulation device 100 to suitthe needs of a particular patient. Such operating parameters define, forexample, pacing pulse amplitude, pulse duration, electrode polarity,rate, sensitivity, automatic features, arrhythmia detection criteria,and the amplitude, waveshape, number of pulses, and vector of eachshocking pulse to be delivered to the patient's heart 102 within eachrespective tier of therapy. One feature of the described embodiments isthe ability to sense and store a relatively large amount of data (e.g.,from the data acquisition system 252), which data may then be used forsubsequent analysis to guide the programming of the device.

Advantageously, the operating parameters of the implantable device 100may be non-invasively programmed into the memory 260 through a telemetrycircuit 264 in telemetric communication via communication link 266 withthe external device 254, such as a programmer, transtelephonictransceiver, or a diagnostic system analyzer. The microcontroller 220activates the telemetry circuit 264 with a control signal 268. Thetelemetry circuit 264 advantageously allows intracardiac electrogramsand status information relating to the operation of the device 100 (ascontained in the microcontroller 220 or memory 260) to be sent to theexternal device 254 through an established communication link 266.

As already mentioned, the stimulation device 100 can further include orcommunicate with one or more physiologic sensors 270. The physiologicsensors 270 may be housed within the case 200, on the surface of thecase 200 or external to the case 200. The one or more physiologicsensors optionally connect to the device 100 via one or more of theconnectors or via other connectors. In some instances, a physiologicsensor may communicate with the microcontroller 220 via a wireless link.For example, a wristwatch physiologic sensor may communicate viaelectromagnetic radiation signals or other signals with a circuit in thedevice 100 (e.g., the telemetry circuit 264). Of course, an implantablephysiologic sensor may also communicate with the device 100 via suchcommunication means.

A physiologic sensor may be used to implement “rate-responsive” therapywhere information sensed is used to adjust pacing stimulation rateaccording to, for example, the exercise state of the patient. Aphysiological sensor may be used to sense changes in cardiac output(see, e.g., U.S. Pat. No. 6,314,323, entitled “Heart stimulatordetermining cardiac output, by measuring the systolic pressure, forcontrolling the stimulation”, to Ekwall, issued Nov. 6, 2001, whichdiscusses a pressure sensor adapted to sense pressure in a rightventricle and to generate an electrical pressure signal corresponding tothe sensed pressure, an integrator supplied with the pressure signalwhich integrates the pressure signal between a start time and a stoptime to produce an integration result that corresponds to cardiacoutput), changes in the physiological condition of the heart, or diurnalchanges in activity (e.g., detecting sleep and wake states). Themicrocontroller 220 can respond to such information by adjusting any ofthe various pacing parameters (e.g., rate, AV Delay, V-V Delay, etc.) oranti-arrhythmia therapy parameters (e.g., timing, energy, leading edgevoltage, etc.).

The exemplary device 100 optionally includes a connector capable ofconnecting a lead that includes a pressure sensor. For example, theconnector 221 optionally connects to a pressure sensor capable ofreceiving information pertaining to chamber pressures or otherpressures. Pressures may be related to cardiac performance and/orrespiration. Pressure information is optionally processed or analyzed bythe CSN module 238.

Commercially available pressure transducers include those marketed byMillar Instruments (Houston, Tex.) under the mark MIKROTIP®. A study byShioi et al., “Rapamycin Attenuates Load-Induced Cardiac Hypertrophy inMice”, Circulation 2003; 107:1664, measured left ventricular pressuresin mice using a Millar pressure transducer inserted through the LV apexand secured in the LV apex with a purse-string suture using 5-0 silk.Various exemplary methods, devices, systems, etc., described hereinoptionally use such a pressure transducer to measure pressures in thebody (e.g., airway, lung, thoracic, chamber of heart, vessel, etc.).

While shown as being included within the stimulation device 100, it isto be understood that the physiologic sensor 270 may also be external tothe stimulation device 100, yet still be implanted within or carried bythe patient. Examples of physiologic sensors that may be implemented indevice 100 include known sensors that, for example, sense pressure,respiration rate, pH of blood, ventricular gradient, cardiac output,preload, afterload, contractility, and so forth. Another sensor that maybe used is one that detects activity variance, wherein an activitysensor is monitored diurnally to detect the low variance in themeasurement corresponding to the sleep state. For a complete descriptionof the activity variance sensor, the reader is directed to U.S. Pat. No.5,476,483 (Bornzin et al.), issued Dec. 19, 1995, which patent is herebyincorporated by reference.

More specifically, the physiological sensors 270 optionally includesensors for detecting movement and minute ventilation in the patient.The physiological sensors 270 may include a position sensor and/or aminute ventilation (MV) sensor to sense minute ventilation, which isdefined as the total volume of air that moves in and out of a patient'slungs in a minute. Signals generated by the position sensor and MVsensor are passed to the microcontroller 220 for analysis in determiningwhether to adjust the pacing rate, etc. The microcontroller 220 monitorsthe signals for indications of the patient's position and activitystatus, such as whether the patient is climbing upstairs or descendingdownstairs or whether the patient is sitting up after lying down.

The stimulation device 100 optionally includes circuitry capable ofsensing heart sounds and/or vibration associated with events thatproduce heart sounds. Such circuitry may include an accelerometer asconventionally used for patient position and/or activity determinations.Accelerometers typically include two or three sensors aligned alongorthogonal axes. For example, a commercially availablemicro-electromechanical system (MEMS) marketed as the ADXL202 by AnalogDevices, Inc. (Norwood, Mass.) has a mass of about 5 grams and a 14 leadCERPAK (approx. 10 mm by 10 mm by 5 mm or a volume of approx. 500 mm³).The ADXL202 MEMS is a dual-axis accelerometer on a single monolithicintegrated circuit and includes polysilicon springs that provide aresistance against acceleration forces. The term MEMS has been definedgenerally as a system or device having micro-circuitry on a tiny siliconchip into which some mechanical device such as a mirror or a sensor hasbeen manufactured. The aforementioned ADXL202 MEMS includesmicro-circuitry and a mechanical oscillator.

While an accelerometer may be included in the case of an implantablepulse generator device, alternatively, an accelerometer communicateswith such a device via a lead or through electrical signals conducted bybody tissue and/or fluid. In the latter instance, the accelerometer maybe positioned to advantageously sense vibrations associated with cardiacevents. For example, an epicardial accelerometer may have improvedsignal to noise for cardiac events compared to an accelerometer housedin a case of an implanted pulse generator device.

The stimulation device 100 additionally includes a battery 276 thatprovides operating power to all of the circuits shown in FIG. 2. For thestimulation device 100, which employs shocking therapy, the battery 276is capable of operating at low current drains for long periods of time(e.g., preferably less than 10 μA), and is capable of providinghigh-current pulses (for capacitor charging) when the patient requires ashock pulse (e.g., preferably, in excess of 2 A, at voltages above 200V, for periods of 10 seconds or more). The battery 276 also desirablyhas a predictable discharge characteristic so that elective replacementtime can be detected.

The stimulation device 100 can further include magnet detectioncircuitry (not shown), coupled to the microcontroller 220, to detectwhen a magnet is placed over the stimulation device 100. A magnet may beused by a clinician to perform various test functions of the stimulationdevice 100 and/or to signal the microcontroller 220 that the externalprogrammer 254 is in place to receive or transmit data to themicrocontroller 220 through the telemetry circuits 264. Trigger IEGMstorage also can be achieved by magnet.

The stimulation device 100 further includes an impedance measuringcircuit 278 that is enabled by the microcontroller 220 via a controlsignal 280. The known uses for an impedance measuring circuit 278include, but are not limited to, lead impedance surveillance during theacute and chronic phases for proper lead positioning or dislodgement;detecting operable electrodes and automatically switching to an operablepair if dislodgement occurs; measuring respiration or minuteventilation; measuring thoracic impedance for determining shockthresholds (HF indications—pulmonary edema and other factors); detectingwhen the device has been implanted; measuring stroke volume; anddetecting the opening of heart valves, etc. The impedance measuringcircuit 278 is advantageously coupled to the switch 226 so that anydesired electrode may be used.

In the case where the stimulation device 100 is intended to operate asan implantable cardioverter/defibrillator (ICD) device, it detects theoccurrence of an arrhythmia, and automatically applies an appropriatetherapy to the heart aimed at terminating the detected arrhythmia. Tothis end, the microcontroller 220 further controls a shocking circuit282 by way of a control signal 284. The shocking circuit 282 generatesshocking pulses in a range of joules, for example, conventionally up toabout 40 J, as controlled by the microcontroller 220. Such shockingpulses are applied to the patient's heart 102 through at least twoshocking electrodes, and as shown in this embodiment, selected from theleft atrial coil electrode 126, the RV coil electrode 132, and/or theSVC coil electrode 134. As noted above, the housing 200 may act as anactive electrode in combination with the RV electrode 132, or as part ofa split electrical vector using the SVC coil electrode 134 or the leftatrial coil electrode 126 (i.e., using the RV electrode as a commonelectrode).

Cardioversion level shocks are generally considered to be of low tomoderate energy level (so as to minimize pain felt by the patient),and/or synchronized with an R-wave and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (i.e., corresponding to thresholds in the range ofapproximately 5 J to approximately 40 J), delivered asynchronously(since R-waves may be too disorganized), and pertaining exclusively tothe treatment of fibrillation. Accordingly, the microcontroller 220 iscapable of controlling the synchronous or asynchronous delivery of theshocking pulses.

In low-energy cardioversion, an ICD device typically delivers acardioversion stimulus (e.g., 0.1 J, etc.) synchronously with a QRScomplex; thus, avoiding the vulnerable period of the T wave and avoidingan increased risk of initiation of VF. In general, if antitachycardiapacing or cardioversion fails to terminate a tachycardia, then, forexample, after a programmed time interval or if the tachycardiaaccelerates, the ICD device initiates defibrillation therapy.

While an ICD device may reserve defibrillation as a latter tier therapy,it may use defibrillation as a first-tier therapy for VF. In general, anICD device does not synchronize defibrillation therapy with any givenportion of a ECG. Again, defibrillation therapy typically involveshigh-energy shocks (e.g., 5 J to 40 J), which can include monophasic orunidirectional and/or biphasic or bidirectional shock waveforms.Defibrillation may also include delivery of pulses over two currentpathways.

Anatomy of Carotid Body and Sinus

Various exemplary techniques described herein relate to the carotid bodyand the carotid sinus. The carotid body is a small cluster ofchemoreceptors and supporting cells located near the bifurcation of thecarotid artery. It responds to changes in the composition of arterialblood, including the partial pressures of oxygen and carbon dioxide aswell as pH, temperature and potassium concentration. The chemoreceptorsresponsible for sensing changes in blood gasses are called glomus cells.The carotid body is involved in both respiratory and cardiovascularcontrol through complex neural pathways, for example, the carotid bodyprovides for a reflex adjustment of respiration according to arterialblood chemistry. Hypoxia (decrease in PO₂), hypercapnia (increase inPCO₂), and acidosis (decrease in pH) increase the rate of chemosensorydischarges in the carotid sinus nerve (CSN) and initiate ventilatory andcardiovascular reflex adjustments.

More specifically, the carotid body responds to a decrease in PaO₂(e.g., atrial hypoxia), ischemia (e.g., from hypotension), an increasein PCO₂ (e.g., >10 mmHg), a decrease in pH (e.g., >about 0.1 to about0.2 pH units), metabolic poisons (e.g., cyanide), drugs (e.g., nicotine,lobeline) and a decrease in blood glucose concentration.

While mechanisms underlying communication between glomus cells of thecarotid body and petrosal ganglion neurons are not completely known,glomus cells, in response to natural and pharmacological stimuli, areexpected to release at least one excitatory transmitter that generatesdischarges in the sensory nerve terminals of petrosal ganglion (PG)neurons.

The carotid sinus is a small oval bulge at the commencement of theinternal carotid artery. At the carotid sinus, the arterial wall is thinand has a rich nerve supply from CN IX as well as some innervation fromCN X. These nerves form an afferent limb of baroreceptor reflex changesin heart rate and blood pressure.

The regulation of arterial blood pressure involves negative feedbacksystems incorporating baroreceptors located in the carotid sinus and inthe aortic arch. The carotid sinus nerve (CSN) branch of CN IXinnervates the carotid sinus, which synapses in the brainstem. Theaortic arch baroreceptors are innervated by the aortic nerve, which thencombines with the vagus nerve (X cranial nerve) traveling to thebrainstem. Arterial baroreceptors are sensitive to stretching of thewalls of the vessels in which the nerve endings lie. Increasedstretching augments the firing rate of the receptors and nerves, andrecruits additional afferent nerves. The receptors of the carotid sinusrespond to pressures ranging from about 60 mm Hg to about 180 mmHg.

Exemplary Arrangement and Method

FIG. 3 shows an exemplary arrangement 310 and an exemplary method 320for acquiring nerve information and acting based at least in part on theacquired nerve information. The arrangement 310 is shown with referenceto the heart, the brain, the aorta, the right common carotid artery andbifurcation, the left common carotid artery and bifurcation, the rightcarotid body and sinus (CB-CS_(R)), the left carotid body and sinus(CB-CS_(L)), and the ninth and tenth cranial nerves. The carotidarteries carry blood to the brain and innervation of the carotid bodyand sinus, which are located near the brain, allow the body to monitorblood flow and blood chemistry and respond accordingly. The tenthcranial nerve (CN X) is the vagus nerve and is primarily associated withparasympathetic activity. The vagus includes the right vagus (X_(R)) andthe left vagus (X_(L)). Various studies indicate that the vagus mayinnervate the carotid body while vagal innervation of the aorticbaroreceptors is well established.

The arrangement 310 includes the implantable device 100 and animplantable lead 110. The lead 110 includes one or more electrodes 144,144′ and may include a bifurcation that allows at least one electrode tobe positioned at, or proximate to, each CSN. In the example of FIG. 3,the lead 110 includes a bifurcation where one branch of the lead allowsfor positioning the electrode 144′ at the right CSN(CSN_(R)) and anotherbranch of the lead allows for positioning the electrode 144 at the leftCSN(CSN_(L)).

The device 100 optionally includes various features of the device 100 ofFIGS. 1 and 2. For example, a lead 108 that includes an electrode 128 isshown positioned in a chamber of the heart, which may be suitable forstimulation and/or acquiring information related to cardiac activity. Ata minimum, the device 100 includes circuitry to acquire nerveinformation such as nerve activity information due topolarization/depolarization of one or more nerve fibers. An exemplaryarrangement optionally includes features for acquiring vagal nerveinformation and glossopharyngeal nerve information.

The exemplary method 320, which may use the arrangement 310, includesacquiring information 324 and acting based at least in part on theacquired information 326. The acquired information may includeinformation from the right CSN and/or the left CSN and optionally one ormore other types of information such as cardiac information, respiratoryinformation, etc. The action 328 may include diagnostic action ortherapeutic action.

Detailed Anatomy

FIG. 4 is an anatomical diagram 400 and a block diagram 410 thatillustrate approximate positions of CN IX and CN X as well ascommunication pathways to the solitary nucleus of the brain. CN IXemerges behind the olive and exits the jugular foramen where it showstwo unipolar-cell ganglia and gives off a tympanic branch which ispartly sensory to the middle ear, partly parasympathetic to the parotidgland via the otic ganglion, CN IX then passes between superior andmiddle constrictors to gain the oropharynx, where it supplies sensationto that mucous membrane including the posterior third of tongue (hencethe name), and taste fibers to the circumvallate papillae.

As already mentioned, a branch of CN IX innervates baroreceptors of thecarotid sinus and chemoreceptors of the carotid body. This branchincludes two sets of afferent fibers. One set ramifies in the wall ofthe carotid sinus (at the commencement of the internal carotid artery),terminating in stretch receptors responsive to systolic blood pressure;these baroreceptor neurons terminate centrally in the medial part of thenucleus solitarius. The second set of afferents in the carotid branchsupplies glomus cells in the carotid body. These nerve endings arechemoreceptors monitoring blood chemistry. The central terminals enterthe dorsal respiratory nucleus. More generally, the nerve supply to thecarotid sinus and body is derived from the carotid branch of CN IX,branches to the carotid body from the inferior ganglion of CN X andsympathetic branches from the superior cervical ganglion.

Afferent nerve activity of CN IX due to a change in blood pressure, adecrease in blood oxygen concentration, a decrease in blood pH, and/oran increase in blood carbon dioxide concentration can cause correctivechanges in ventilation so as to maintain blood gas and pH homeostasis.

FIG. 5 shows a more detailed diagram of a cell unit of the carotid body500 and a block diagram of a process 510. Sustentacular cells (modifiedSchwann cells, labeled SC) are intimately surrounded and interlaced witha rich network of capillaries and venules. Clusters of cells are called“zellballen”, and can generally be separated into “light” cell (labeledLC) and “dark” cell (labeled DC) subpopulations, referring to thedensity of intracellular neurosecretory granules. Chief cells aremembers of the amine precursor and uptake decarboxylase (APUD) family,recently referred to as the DNES (diffuse neuroendocrine system). Theterm glomus was applied originally because it was erroneously thoughtthat the chief cells arose from specialized pericytes as seen in truearteriovenous complexes (“glomus complexes”); noting that the termglomus is still commonly used.

A cell unit of a carotid body generates afferent nerve activityresponsive to blood chemistry. For example, in the process 510, adecrease in oxygen concentration, a decrease in pH and/or an increase incarbon dioxide can cause cells of the unit to release dopamine, whichincreases CSN activity and provokes centrally-mediated cardiopulmonaryresponses. While various examples discuss afferent nerve activity, somestudies indicate that the carotid body includes efferent innervation,which may be via the CSN. Thus, various exemplary techniques may includeacquiring efferent nerve information (e.g., via sensing, filtering,analyzing, etc.).

Exemplary Methods and Arrangements

FIG. 6 shows exemplary scenarios 600 for acquiring nerve information,analyzing such information and acting based at least in part on theacquired information and/or the analysis thereof. Scenario I 610includes an acquisition block 612 that acquires nerve information fromCSN_(R) or CSN_(L). The acquisition may occur via use of one or moreelectrodes capable of sensing nerve activity (e.g., cuff electrodes,etc.). For example, an implantable device may include one or more cuffor plate electrodes that can be placed around, in, and/or on the nervewith or without an anchoring mechanism to avoid dislodgment.

An analysis block 614 analyzes acquired nerve information. For example,an analysis block 614 may include one or more filters (e.g., high pass,low pass, band pass, etc.), a recognition algorithm, a Bayesian orneural network algorithm, etc., that can determine if the acquired nerveinformation indicates a change in physiologic condition (e.g., a changein blood pressure and/or blood chemistry).

An action block 616 may act on nerve information and/or an analysis ofnerve information. For example, if a nerve signal amplitude or frequencyexceeds a certain limit associated with blood pressure, then the actionblock 616 may call for an adjustment to a therapy such as a cardiacpacing therapy to control blood pressure. Where indicia of a change inphysiology are not amenable to a simple limit approach, then an analysismay be used to determine whether a change has occurred in one or morephysiological conditions. The analysis block 614 may perform such ananalysis and then instruct the action block 616 to take appropriateaction.

Scenario II 620 includes an acquisition block 622 that acquires nerveinformation from both CSN_(R) and CSN_(L). In scenario II 620, ananalysis block 624 may use a differential approach. For example, certainphysiological conditions may be indicated by a difference in nerveactivity at CSN_(R) and CSN_(L). An analysis may simply subtract aCSN_(R) electroneurogram from a CSN_(L) electroneurogram. Alternatively,a sensing arrangement may provide for acquisition of a differentialsignal (e.g., using a common electrode or common acquisition circuitry).Referring to FIG. 3, a small lime differential may exist between a bolusof blood exiting the left ventricle and a portion of the bolus reachingthe right carotid body and a portion of the bolus reaching the leftcarotid body. Such a time difference (Δt) may be used in synchronizingnerve activity with blood exiting the left ventricle. For example, if adecrease in blood oxygen causes an increase in nerve activity at CSN_(R)at time t₁ then an increase in nerve activity at CSN_(L) may be expectedto occur at time t₁+Δt.

The action block 626 of scenario II 620 may act on nerve informationand/or an analysis of nerve information. For example, if a delay betweenCSN_(R) and CSN_(L) changes or exceeds a limit, then the action block626 may issue an alert to a patient or a care provider. In all of thescenarios of FIG. 6, an action may simply store information for analysisor review at a later time (e.g., by an implantable device and/or anexternal device).

Scenario III 630 includes an acquisition block 632 that acquires CSN_(R)or CSN_(L) information and other information. Other information may becardiac activity information, patient activity information, patientposition information, respiratory information, autonomic nerveinformation, etc. In scenario III 630, the analysis block 634 may usethe nerve information to confirm or assess the other information. Forexample, where the other information is acquired using a pressure sensorfor sensing blood pressure, the nerve information may be used to confirma change in blood pressure. In another example, photoplethysmography maybe used to sense blood gas levels and nerve information may be used toconfirm such levels. In yet another example, impedance plethysmographymay be used to monitor changes in blood volume (or edema) and nerveinformation may be used to assess consequences of a change in bloodvolume.

The action block 636 may initiate an action based on an analysis thatuses nerve information to confirm or assess other information. Theaction block 636 may store information, results of an analysis and/orcall for therapeutic action.

The scenario IV 640 includes an acquisition block 642 that acquiresCSN_(R), CSN_(L) and other information. For example, the otherinformation may be CN X_(R) and CN X_(L) nerve information acquiredusing the same implantable system used to acquire the CSN_(R) andCSN_(L) information. The analysis block 644 may analyze such informationin any of a variety of manners to allow an action block 646 to takeappropriate action. Referring again to FIG. 3, branches of the vagalnerve (X_(R) and X_(L)) innervate the baroreceptors of the aortic arch.Information acquired from these branches may be used in conjunction withinformation from CSN_(R) and CSN_(L) to assess arterial blood pressure.Given the implantable device 100, such an assessment may be used toadjust a cardiac pacing therapy to control blood pressure. Informationmay be acquired during or after control to provide a feedback loop thatoptionally enhances the cardiac pacing therapy's ability to controlblood pressure.

FIG. 7 shows an example 611 using scenario I 610 and an example 631using scenario III 630. In the example 611 for scenario I 610, theacquisition block 612 acquires an electroneurogram of CSN_(R) activity.The analysis block 614 analyzes the electroneurogram and determines thatblood oxygen concentration and pH decreased while blood carbon dioxideconcentration increased. The analysis also determines that certain nerveinformation cannot be readily identified or associated with a change inphysiological condition (see “?” in FIG. 7). Based at least in part onthe analysis, the action block 616 instructs an implantable cardiacpacing device to increase heart rate.

In the example 631 for scenario III 630, the acquisition block 632acquires CSN_(L) nerve activity and activity from a feeding sensor. Inthis example, the analysis block 634 determines that the CSN_(L) nerveactivity indicates a low blood glucose concentration and that feedinghas not occurred for about 6 hours (noting that the scales on theCSN_(L) plot and feeding plot may differ). In response, the action block636 calls for issuance of an alert to commence feeding due to low bloodglucose concentration.

FIG. 8 shows an example 621 for scenario II 620 of FIG. 6. In thisexample, the acquisition block 622 acquires nerve information for bothCSN_(R) and CSN_(L). The analysis block 624 determines a differentialbased on the acquired nerve information. In turn, the action block 626issues an alert to instruct a patient to change body position. Forexample, a delay between right side and left side nerve information mayindicate an imbalance in blood flow. To compensate for the imbalance, anexemplary device may vibrate or deliver a stimulus (e.g., at a certainfrequency) that notifies a patient to change body position to therebybalance blood flow. In general, the heart experiences more force when apatient lies on her left side compared to lying on her right side. Suchforce may cause an imbalance in blood flow (e.g., pressure) in thecarotid arteries, the degree of which can be determined using CSN_(R)and CSN_(L) activity information.

With respect to the differential, a plot labeled “A” demonstrates adelay in nerve activity where right side activity commences earlier thanleft side activity and where left side activity persists after rightside activity terminates. Amplitudes, morphology, frequencies, etc., maybe used to determine a differential suitable for diagnostic ortherapeutic action.

FIG. 9 shows various exemplary methods and arrangements of equipment900. The methods 910, 930, 950 are suitable for associating nerveactivity with a physiological condition. Various exemplary arrangementsor systems are shown with respect to an implantable device capable ofacquiring CSN information 960, 970, 980.

The glucose test method 910 establishes a relationship between nerveactivity and blood glucose concentration. An administration block 912causes a patient's blood glucose concentration to decrease. For example,a care provider or patient may administer an injection of insulin, ananabolic hormone that controls cellular intake of certain substances,most prominently glucose in muscle and adipose tissue, as well asglycogen synthesis, glycogen storage in liver and muscle cells, fattyacid synthesis in fat cells, increase potassium uptake among othereffects. Overall, an increase in CSN activity or a change in CSNactivity may be expected in response to an insulin induced decrease inblood glucose concentration (hypoglycemia). Fasting may achieve asimilar decrease, especially for a diabetic patient. Further, the method910 may include administration of a catabolic hormone or a carbohydrateto increase blood glucose concentration. Using such techniques, ananalysis block 916 may analyze a certain portion of an electroneurogram(e.g., marked by administration of two opposing treatments) to establisha relationship between blood glucose concentration and CSN activity, perblock 918.

An exemplary method may use the relationship between blood glucoseconcentration and CSN activity to control therapy. For example, animplantable device may detect hypoglycemia and issue a signal for apatient or care provider to take appropriate action (see, e.g.,arrangements 960, 970, 980). Where a patient has an implanted insulinpump that delivers insulin according to a schedule or zero-order basis,detection of hypoglycemia may cause the pump to cease delivery ofinsulin (see, e.g., arrangement 980). For example, some pumps deliver abasal dose on an approximately zero-order basis (e.g., substantiallyconstant basis). CSN information may be used to adjust such delivery. Ininstances where a glucometer is used, CSN information may be used toconfirm or assess a glucometer reading. Some glucometers includecircuitry for wireless communication with an implanted insulin pump. CSNinformation may be acquired by an implanted insulin pump or otherwisecommunicated to an implanted insulin pump or an external device such asa glucometer (see, e.g., arrangements 970, 980).

While the above examples mention use of a glucometer in conjunction withnerve information, an accelerometer or other sensor capable of detectingsteadiness or patient activity may be used additionally or alternativelyto determine if a patient is dizzy, losing consciousness, etc. (see,e.g., arrangement 980, device 100 of FIGS. 1 and 2).

Other types of therapy related to blood glucose or insulin concentrationmay include activation or blocking of one or more autonomic nervesrelated to pancreatic activity (e.g., pancreatic vagal stimulation).

The gas test method 930 establishes a relationship between nerveactivity and blood gas(es) concentration(s) and optionally blood pH(hydrogen ion concentration). An administration block 932 causes apatient's blood oxygen level to decrease and blood carbon dioxide levelto increase. For example, patient may hold her breath or exercise tocause such changes in blood gas concentrations. After or before suchadministration, a patient or a care provider may administer oxygen(e.g., oxygen mask or positive pressure mask) to the patient to increasethe blood oxygen concentration. Using such techniques, an analysis block936 may analyze a certain portion of an electroneurogram (e.g., markedby administration of two opposing treatments) to establish arelationship between blood gas(es) concentration(s) and CSN activity,per block 938. Such a relationship or relationships may be used indetection or treatment of respiratory disorders such as apnea, which isdiscussed further below.

The blood pressure test method 950 establishes a relationship betweennerve activity and blood pressure. An administration block 952administers a tilt test or other test that causes a patient's bloodpressure to change. Using such techniques, an analysis block 956 mayanalyze a certain portion of an electroneurogram (e.g., marked byadministration of two opposing states) to establish a relationshipbetween blood pressure and CSN activity, per block 958. Such arelationship or relationships may be used in detection or treatment ofvarious conditions including cardiopulmonary (e.g., congestive heartfailure) and respiratory disorders (e.g., apnea, which is discussedbelow).

Apnea includes central sleep apnea (CSA) and obstructive sleep apnea(OSA). During obstructive apneas, chemoreflex activation by hypoxemia(low PO₂) and hypercapnia (high PCO₂) can cause even further increasesin sympathetic activity, with recurrent surges in blood pressure mostnotable at the end of apneic events. Blood pressure may increase up to250/130 mm Hg even though the patient is normotensive during wakefulness(see, e.g., Somers et al., “Sympathetic neural mechanisms in obstructivesleep apnea”. J Clin Invest. 1995; 96:1897-1904).

Patients treated with continuous positive airway pressure (CPAP, whichincreases PO₂) after apneic events demonstrate attenuation of theincrease in sympathetic nervous system activity while patients withuntreated OSA have higher sympathetic nervous system activity comparedwith controls, even when awake and normoxic. Patients with untreated OSAalso have faster heart rates, blunted heart rate variability, andincreased blood pressure variability during normoxic daytimewakefulness.

As described herein, the blood gas test method 930 and/or the bloodpressure test method 950 may be used in treatment of apnea. For example,the gas test method 930 and/or the blood pressure test method 950 may beperformed and resulting relationships used for administering anti-apneatherapy and/or apnea breaking therapy. An anti-apnea therapy may respondto nerve activity indicative of decreasing PO₂ or increasing PCO₂ whilean apnea breaking therapy may respond to nerve activity indicative of achange in blood pressure. An exemplary method may use both approachesand optionally include use of other information to call for or adjust anapnea therapy. An apnea therapy may include delivery of stimulation totissue or other action (e.g., vibration, etc.), Apnea therapies thatstimulate tissue may stimulate one or more of the myocardium, thephrenic nerve, the diaphragm, the upper air muscles, etc.

The exemplary arrangement 970 may include an implantable device thatacquires CSN information and that communicates with an external devicefor delivery of an apnea therapy (e.g., a positive airway pressuredevice). The exemplary arrangement 980 may include an implantable devicethat acquires CSN information and that communicates with anotherimplantable device for delivery of an apnea therapy (e.g., a phrenicnerve stimulation device).

With respect to OSA, maintenance of upper airway patency ultimatelydepends on a balance between stabilizing and collapsing forces. Factorsinvolved in effective stabilization of upper airway structures includeupper airway neuromuscular activity, physiological properties of upperairway muscles, effectiveness of upper airway muscle contraction andmechanical coupling of upper airway muscles to surrounding soft tissues.

Phasic activity of upper airway muscles is known to precede that ofrespiratory muscles in normal patients as well as those affected by OSA.The contraction of upper airway dilators generates the only stabilizingforce that opposes a series of collapsing forces, including the effectsof gravity-induced posterior displacement of upper airway structures,the negative inspiratory upper airway transmural pressure gradient, andsurface tension forces. Maintenance or alteration of upper airwaypatency may consider contraction of dilators as well as characteristicsof the collapsing forces. As the right and left CSN are locatedproximate to the upper airway, an exemplary device may acquire CSNinformation and optionally other information and deliver an apneatherapy that includes stimulation of a nerve or tissue to promote upperairway patency.

As described herein, sensing of nerve activity, sensing of muscleactivity, delivery of energy to one or more nerves and/or delivery ofenergy to one or more muscles may be used to maintain upper airwaypatency. Referring to FIG. 4, the upper airway anatomy is shown alongwith pathways of CN IX, CN X and CN XII. An exemplary method may acquireinformation from one or more of these nerves. Such information may beused in conjunction with an apnea treatment therapy (e.g., prevention,breaking or recovery).

With respect to respiration or autonomic tone, which may be consideredother information for use in conjunction with CSN information, animplantable device may include features for measuring respiratory sinusarrhythmia (RSA). RSA is a natural cycle of arrhythmia that occursthrough the influence of breathing on autonomic tone. During inspirationvagus nerve activity is impeded, which shifts the autonomic tone towardssympathetic. In response, the RR interval shortens, i.e., heart rateincreases. During expiration, the autonomic tone shifts towardparasympathetic and the RR interval lengthens, i.e., heart ratedecreases. While research indicates that both parasympathetic andsympathetic mechanisms contribute to RSA, RSA is primarily due tochanges in parasympathetic activity.

As described herein, sensing heart rate or RR interval may be used todetermine one or more respiratory characteristics. Further, sensingheart rate or RR interval may be used to estimate autonomic tone orother autonomic characteristic. For example, if there is little changein heart rate over one or more respiratory cycles, then the autonomictone may be shifted toward sympathetic. Yet further, excessive RSA mayindicate an overactive parasympathetic system.

As already mentioned, the CSN responds to potassium concentration. Anexemplary method may include administration potassium (e.g., saltsolution) to excite the CSN. Further, administration of potassium may beused to enhance CSN activity caused by hypoxia. Acquisition and analysisof nerve activity may be used to associate such activity with bloodpotassium concentration. A relationship between CSN activity and bloodpotassium concentration may be used to diagnose renal condition and/orfor delivery of a renal therapy.

FIG. 10 shows a block diagram of various exemplary methods 1000 suitablefor use in an exemplary implantable device that can acquire CSNinformation. In an acquisition block 1002, an implantable deviceacquires one or more electroneurograms (ENGs) from the right and/or leftCSN. In an extraction or analysis block 1004, specific measurements areextracted from the one or more electroneurograms. The device may beconfigured to sense such information or to acquire such information fromanother device. The extracted measurements may include blood gas (e.g.,oxygen, carbon dioxide), ion concentrations (e.g., K⁺, Na⁺, H⁺), bloodpressure, ventilation rate or other measurements. An implantable devicemay be configured to extract such measurements from one or moreelectroneurograms or to acquire extracted measurements from anotherdevice. In the latter instance, the other device may decide whichextracted measurements to communicate.

According to the diagram 1000, measurements of the oxygen, carbondioxide, glucose, potassium, pH, blood pressure, and ventilation rateare extracted from one or more electroneurograms of the right and/orleft CSN. Based at least in part on one or more of these measurements,an implantable device may detect episodes of different physiologicalstates and treat an episode with an appropriate therapeutic response.

An exemplary implantable device may include any of the features of thedevice 100 of FIGS. 1 and 2 and may be a pacemaker, a defibrillator, ora defibrillator and a pacemaker. As shown in FIG. 2, the device 100includes a specialized processing unit (module 238) that can utilizeinformation extracted from the right and/or left CSN, for example, tomaintain homeostasis of a patient. As already described, the device 100may be capable of controlling a variety of pacing electrodes and/ordevices to change cardiac pacing, phrenic nerve pacing, parasympatheticnervous system pacing, and/or sympathetic nervous system pacing. Thedevice 100 may also include circuitry to alert a patient about events.In general, the device 100 includes memory capable of storinginformation where a care provider or patient may retrieve theinformation.

The module 238 may include an algorithm to process nerve informationusing techniques such as analog filters, digital filters, digital signalprocessing, and/or classification algorithms (e.g., neural networks,genetic algorithms, wavelet decomposition, Bayesian classifiers, and kthnearest neighbor).

An exemplary device may use electrical activity of the right and/or leftCSN associated with ventilation rate, oxygen concentration, carbondioxide concentration, potassium concentration, glucose concentration,blood pressure, pH, etc., to detect episodes of sleep apnea (lowventilation, low oxygen, and high carbon dioxide), increased/decreasedlevels of metabolic demand (high ventilation, low oxygen, and highcarbon dioxide), episodes of hypoglycemia (co-morbidity ofcardiovascular disease), hypertension, and other episodes such ashyperkalemia, acidemia, hypoxia, and hypercapnia.

An exemplary implantable device may use one or more extractedmeasurements for any of a variety of purposes. In the example of FIG.10, four exemplary methods 1010, 1020, 1030 and 1040 are shown that maybe implemented by an implantable device configured to call for variousactions and optionally perform such actions.

Sleep apnea, as discussed above, a co-morbidity of heart failure, canlead to neurocognitive deficits, daytime fatigue, pauses in breathing,arterial oxygen desaturation, and cardiovascular consequences such ashypertension and stroke. Sleep apnea causes a decrease in ventilationrate, oxygen concentration, and pH, and an increase in carbon dioxideconcentration.

The exemplary method 1010 can diagnose and treat sleep apnea. In ameasurement analysis block 1012, the method 1010 can, for example,determine trends based on extracted measures. In turn, a diagnosis block1014 uses the analyzed information to diagnose patient condition. Inthis example, a decrease in ventilation rate, an increase in carbondioxide concentration, a decrease in oxygen concentration and a decreasein blood pH are indicative of sleep apnea. The diagnosis can then beused to call for appropriate therapeutic action per an action block1016. For example, phrenic nerve stimulation, diaphragm activation, orother action may counter sleep apnea.

When combined with the acquisition block 1002 and the extraction block1004, the exemplary method 1010 provides for diagnosing sleep apnea byacquiring an electroneurogram of carotid sinus nerve activity, analyzingthe electroneurogram for at least one of a decrease in ventilation rate,an increase in blood carbon dioxide concentration, a decrease in bloodoxygen concentration and a decrease in blood pH and, based at least inpart on the analyzing, determining if sleep apnea exists. Such a methodoptionally includes, if sleep apnea exists, calling for and/ordelivering a therapy to treat sleep apnea.

An exemplary implantable device includes features perform the method1010. For example, a device may include features to detect a decrease inventilation rate, oxygen concentration, and pH, and an increase incarbon dioxide concentration and optionally to classify this response assleep apnea or a particular type of sleep apnea. In turn, the device maycall for action to counteract the sleep apnea episode such as increasephrenic nerve pacing.

Increases in metabolic demand result in increased carbon dioxideproduction, increased ventilation, increased demand for oxygen andglucose, and increased heart rate. The exemplary method 1020 candiagnose and respond to an increase in metabolic demand. In ameasurement analysis block 1022, the method 1020 can, for example,determine trends based on extracted measures. In turn, a diagnosis block1024 uses the analyzed information to diagnose patient condition. Inthis example, an increase in ventilation rate and carbon dioxideconcentration and a decrease in oxygen concentration and glucoseconcentration are indicative of increased metabolic demand. Thediagnosis can then be used to call for appropriate therapeutic actionper an action block 1026. For example, the action block 1026 may callfor an increase in cardiac pacing rate.

When combined with the acquisition block 1002 and the extraction block1004, the exemplary method 1020 provides for diagnosing an increase inmetabolic demand by acquiring an electroneurogram of carotid sinus nerveactivity, analyzing the electroneurogram for at least one of a decreasein ventilation rate, an increase in blood carbon dioxide concentration,a decrease in blood oxygen concentration and a decrease in blood glucoseconcentration and, based at least in part on the analyzing, determiningif metabolic demand increased. Such a method optionally includes, ifmetabolic demand increased, calling for delivery and/or delivering atherapy to increase heart rate.

An exemplary implantable device includes features perform the method1020. For example, an implantable device may detect a wider variety ofmetabolic demands when compared to a conventional pacemaker with amotion-based patient activity circuit. An exemplary device may acquireCSN information indicative of increased metabolic demands as a result ofnon-physical activity (intense concentration, stress, excitement, etc).For example, such a device may include features to measure an increasein ventilation rate, an increase in carbon dioxide concentration, adecrease in oxygen concentration, and a decrease in glucoseconcentration and classify this response as increased metabolic demand.In response, the device may instruct a cardiac pacemaker or cardiacpacing feature to increase cardiac pacing rate to compensate for theincreased metabolic demand.

Diabetes, as discussed above, a co-morbidity of heart failure, isassociated with hypertension, bradycardia, and tachycardia. Studiesindicate that strict glucose regulation delays long-term complicationsof diabetes. Hypoglycemia is characterized by shaking, sweating,palpitations, fatigue, confusion, behavioral changes, and evenunconsciousness. Some diabetics have a difficult time determining whenthey are having hypoglycemic episodes, which can increase the tendencyto stay at hyperglycemic levels and, hence, hasten long-termcomplications of diabetes.

The exemplary method 1030 can diagnose and respond to hypoglycemia. In ameasurement analysis block 1032, the method 1030 can, for example,determine trends based on extracted measures. In turn, a diagnosis block1034 uses the analyzed information to diagnose patient condition. Inthis example, a decrease in blood glucose concentration and blood pHconcentration are indicative of hypoglycemia. The diagnosis can then beused to call for appropriate therapeutic action per an action block1036. For example, the action block 1036 may call for issuance of apatient alert signal and an increase in sympathetic activity (e.g., anincrease in stimulation to a sympathetic nerve).

When combined with the acquisition block 1002 and the extraction block1004, the exemplary method 1030 provides for diagnosing hypoglycemia byacquiring an electroneurogram of carotid sinus nerve activity, analyzingthe electroneurogram for at least one of a decrease in blood glucoseconcentration and a decrease in blood pH and, based at least in part onthe analyzing, determining if hypoglycemia exists. Such a methodoptionally includes, if hypoglycemia exists, issuing an alert, callingfor delivery of a therapy to increase sympathetic tone and/or deliveringsuch a therapy.

An exemplary implantable device includes features perform the method1030. For example, an implantable device may include features to detectlow glucose and pH levels, based at least in part on CSN information,and to stimulate the sympathetic nervous system to hinder insulinrelease and to hasten blood glucose release. Such a device may alsoalert a patient as to low blood glucose levels (e.g., by an audio,vibratory, stimulation, or other feedback mechanism).

Hypertension is another co-morbidity of heart failure. As a result ofchronic hypertension, the heart hypertrophies to maintain cardiacoutput, Over time, the heart hypertrophies to a point where the size ofthe ventricles shrinks and cardiac output decreases.

The exemplary method 1040 can diagnose and respond to hypertension. In ameasurement analysis block 1042, the method 1040 can, for example,determine trends based on extracted measures. In turn, a diagnosis block1044 uses the analyzed information to diagnose patient condition. Inthis example, an increase in blood pressure is indicative ofhypertension. The diagnosis can then be used to call for appropriatetherapeutic action per an action block 1046. For example, the actionblock 1046 may call for an increase in parasympathetic activity (e.g.,by a decrease in stimulation to a sympathetic nerve or by a change insympathetic neural stimulation to block the neural pathway).

When combined with the acquisition block 1002 and the extraction block1004, the exemplary method 1040 provides for diagnosing hypertension byacquiring an electroneurogram of carotid sinus nerve activity, analyzingthe electroneurogram for at least a change in blood pressure and, basedat least in part on the analyzing, determining if hypertension exists.Such a method optionally includes if hypertension exists, calling fordelivery of or delivering a therapy to decrease sympathetic tone and/orcalling for delivery of or delivering a therapy to increaseparasympathetic tone.

An exemplary implantable device includes features perform the method1040. For example, an implantable device may acquire CSN information anduses such information to detect high blood pressure and call forstimulation of the parasympathetic nervous system and/or block thesympathetic nervous system to reduce blood pressure.

An exemplary implantable device suitable for implementation of any ofthe various methods 1010, 1020, 1030, 1040 includes a processor, a leadbearing one or more electrodes positionable to sense electrical activityof the right carotid sinus nerve or the left carotid sinus nerve andcontrol logic, operable in conjunction with the processor, to analyzethe sensed electrical activity for chemosensory information orbarosensory information. Such a device may include one or moreelectrodes that allow for sensing nerve activity in a neural pathwaybetween the right carotid body or left carotid body and the brain. Thecontrol logic may include features to diagnose sleep apnea, diagnose anincrease in metabolic demand, diagnose hypoglycemia, and/or diagnosehypertension.

FIG. 11 shows an exemplary method 1100 to acquire information using onedevice and to analyze the acquired information using a different device.For example, an implantable device (e.g., the device 100 of FIGS. 1 and2) may acquire information while an external device 960 or 970 mayanalyze information acquired by the implantable device. In analternative arrangement, a patient is fitted with two implantabledevices where a first device acquires information and a second device980 analyzes information acquired by the first device.

Per the method 1100, in an acquisition block 1102, an implantable deviceacquires information such as nerve activity information from the rightand/or left CSN. A storage block 1104 stores the acquired information,for example, as raw data or processed data with optional time markers,etc. During a clinical visit, telephonic communication, etc., anotherdevice 960, 970 or 980 pulls the stored information per a communicationblock 1106. The device 960, 970 or 980 may then, in an analysis block1108, analyze the information pulled from the other, implantable device.A program block 1110 may be used to program the other, implantabledevice based at least in part on the analysis of the information. Forexample, a programmer for an implantable device may include telemetrycircuitry, a processor and control logic for performing steps 1106, 1108and 1110. Such a process may occur according to a schedule, according tooccurrence of an event (e.g., arrhythmia, apnea, etc.), or according toa clinician's command. The analysis may help diagnose patient conditionand be beneficial in selecting a therapy and/or adjusting a therapy totreat such a condition. In general, carotid sinus nerve information maybe acquired at various times, optionally stored and analyzed todetermine if a condition is worsening, improving or staying the same.

An exemplary method includes acquiring an electroneurogram of the rightcarotid sinus nerve or the left carotid sinus nerve, storing theelectroneurogram in memory of an implantable device, communicating thestored electroneurogram to another device and analyzing theelectroneurogram for at least one of chemosensory information andbarosensory information. Such a method may further include calling forone or more therapeutic actions based at least in part on the analyzingand/or instructing the implantable device to call for one or moretherapeutic actions based at least in part on the analyzing. Such amethod may compare at least one of the chemosensory information and thebarosenory information to historic information, for example, to make adiagnosis or to aid in selecting a therapy and/or adjusting a therapy.With respect to making a diagnosis, the diagnosis may include sleepapnea, an increase in metabolic demand, hypoglycemia and hypertension.

An exemplary system includes an implantable device with a processor,memory, a telemetry circuit, a lead bearing one or more electrodespositionable to sense electrical activity of the right carotid sinusnerve or the left carotid sinus nerve and control logic, operable inconjunction with the processor, to store in the memory sensed electricalactivity or information derived from the sensed electrical activity andanother device (e.g., implantable or external) with a processor, memory,a telemetry circuit and control logic to download, via the telemetrycircuit, sensed electrical activity or information derived from thesensed electrical activity from the memory of the implantable device.The download device may include control logic to make a diagnosis basedat least in part on the downloaded sensed electrical activity orinformation derived from the sensed electrical activity and/or includecontrol logic to program one or more operational parameters of theimplantable device.

As described herein, the CSN includes many neurons carrying varioustypes of information. To extract or identify particular information,filtering or other techniques (e.g., neural networks, DSP filters,analog filters, wavelets, matched filters, clustering, etc.) may beused, for example, to uncover activity associated with pH, bloodpressure, glucose concentration, etc. Techniques to extract or identifyparticular information may include use of certain electrode designs orconfigurations.

An exemplary method may identify regions of neurons as carryingparticular information. For example, an exemplary method may determinethat a region of neurons associated with blood pressure are groupedtowards one side of the CSN while neurons carrying informationassociated with oxygen concentration are grouped to another side, etc.An electrode or electrode array that records activity from a certainportion or portions of the nerve may be used to extract particularinformation. Where an electrode array allows for multiple electrodeconfigurations, one configuration may be selected to sense one type ofnerve activity and another configuration selected to sense another typeof nerve activity. Where appropriate, sensing may occur at more than onesite along the right CSN and/or the left CSN.

In general, the neuronal diameter population varies within a nerve, anda neuron's diameter often dictates propagation speed of an actionpotential such that the speed of the action potential increases as thediameter of the neuron increases. Faster action potential propagationspeeds have a higher characteristic frequency than a slower propagationspeed. An exemplary analysis technique analyzes a CSN electroneurogramto separate out different diameter neurons based on frequency orfrequencies (e.g., characteristic frequencies). Also, neurons within anerve are typically grouped into fascicles based on the origin of theneurons. As fascicles are spatially distributed within a nerve, anexemplary technique may determine fascicle location by recording nerveactivity with more than one electrode. By determining the signal'scharacteristic frequency and fascicle, an exemplary technique mayassociate a particular type of receptor with a particular type of nerveactivity.

An exemplary method may include delivering stochastic noise (e.g.,random noise) to a carotid sinus nerve or other nerve as a therapeutictechnique to alter a nerve signal. Such a method may deliver the noisesub-threshold to a particular population of nerve fibers of the carotidsinus nerve or other nerve. Certain noise may suffice for a particularpopulation while a different noise may suffice for another population.

Conclusion

Although exemplary methods, devices, systems, etc., have been describedin language specific to structural features and/or methodological acts,it is to be understood that the subject matter defined in the appendedclaims is not necessarily limited to the specific features or actsdescribed. Rather, the specific features and acts are disclosed asexemplary forms of implementing the claimed methods, devices, systems,etc.

1. A method comprising: administering one or more treatments to a patient to change the patient's arterial blood pressure; acquiring at least one electroneurogram of at least a first carotid sinus nerve activity; analyzing the at least one electroneurogram to determine a relationship between said patient's arterial blood pressure and said patient's carotid sinus nerve activity, wherein determining the relationship comprises filtering the at least one electroneurogram to determine one or more neurons or regions of neurons of the carotid sinus nerve carrying information associated with arterial blood pressure; and sensing a second carotid sinus nerve activity and using the second carotid sinus nerve activity and the determined relationship between carotid sinus nerve activity and arterial blood pressure to control delivery of a therapy to treat a cardiopulmonary disorder and/or a respiratory disorder.
 2. The method of claim 1 wherein the determining comprises filtering the at least one electroneurogram to determine chemosensory information.
 3. The method of claim 1 wherein the determining comprises filtering the at least one electroneurgram to determine barosensory information.
 4. The method of claim 3 wherein the barosensory information comprises arterial blood pressure information.
 5. The method of claim 1 wherein the therapy comprises cardiac pacing therapy.
 6. The method of claim 1 wherein the therapy comprises blocking one or more sympathetic nerves and wherein the disorder is hypertension.
 7. The method of claim 1 wherein the therapy comprises stimulating one or more parasympathetic nerves and wherein the disorder is hypertension.
 8. The method of claim 1 further comprising: sensing heart rate over one or more respiratory cycles; determining whether heart rate increases, decreases, or stays substantially at the same rate over one or more respiratory cycles; if heart rate stays substantially at the same rate over one or more respiratory cycles, determining that the autonomic tone has shifted toward sympathetic; and if heart rate substantially increases over one or more respiratory cycles, determining that the autonomic tone has shifted toward parasympathetic.
 9. The method of claim 1 further comprising administering a second treatment to the patient to change the patient's arterial blood pressure in an opposite direction, wherein analyzing the at least one electroneurogram comprises analyzing the portions of the at least one electroneurogram marked by administration of the two opposing treatments to determine a relationship between said patient's arterial blood pressure and said patient's carotid sinus nerve activity.
 10. The method of claim 1 wherein the at least one electroneurogram is acquired using an electrode array configured to allow for multiple electrode configurations.
 11. The method of claim 10 wherein one electrode configuration is selected to sense one type of nerve activity and a second different electrode configuration is selected to sense a second different type of nerve activity.
 12. The method of claim 10 wherein filtering the at least one electroneurogram comprises determining fascicle location by recording nerve activity with more than one electrode.
 13. The method of claim 10 wherein filtering the at least one electroneurogram comprises separating out different diameter neurons based on one or more frequencies.
 14. The method of claim 10 wherein filtering the at least one electroneurogram comprises associating a particular type of receptor with a particular type of nerve activity.
 15. The method of claim 1 wherein administering one or more treatments comprises administering two opposing treatments, wherein one treatment increases blood pressure, and wherein the opposing treatment decreases blood pressure.
 16. The method of claim 15 wherein analyzing the at least one electroneurogram comprises analyzing portions of the electroneurogram marked by administration of the two opposing treatments.
 17. The method of claim 1 wherein the therapy comprises delivery of energy to one or more nerves or one or more muscles.
 18. The method of claim 1 wherein the therapy comprises delivery of energy to one or more nerves and to one or more muscles.
 19. The method of claim 1 wherein the therapy comprises treatment with a continuous airway pressure device.
 20. One or more non-transitory computer-readable media comprising processor executable instructions for performing the acquiring and the analyzing of the method of claim
 1. 